Abstract
Macrophages are a diverse group of phagocytic cells acting in host protection against stress, injury, and pathogens. Here, we show that the scavenger receptor SR-A6 is an entry receptor for human adenoviruses in murine alveolar macrophage-like MPI cells, and important for production of type I interferon. Scavenger receptors contribute to the clearance of endogenous proteins, lipoproteins and pathogens. Knockout of SR-A6 in MPI cells, anti-SR-A6 antibody or the soluble extracellular SR-A6 domain reduced adenovirus type-C5 (HAdV-C5) binding and transduction. Expression of murine SR-A6, and to a lower extent human SR-A6 boosted virion binding to human cells and transduction. Virion clustering by soluble SR-A6 and proximity localization with SR-A6 on MPI cells suggested direct adenovirus interaction with SR-A6. Deletion of the negatively charged hypervariable region 1 (HVR1) of hexon reduced HAdV-C5 binding and transduction, implying that the viral ligand for SR-A6 is hexon. SR-A6 facilitated macrophage entry of HAdV-B35 and HAdV-D26, two important vectors for transduction of hematopoietic cells and human vaccination. The study highlights the importance of scavenger receptors in innate immunity against human viruses.
Highlights
Macrophages are a diverse population of innate immune cells
Macrophages are a diverse group of phagocytic cells acting in host protection against stress, injury, and pathogens
In a series of robust experimentation, we show that adenoviruses use scavenger receptors (SRs)-A6 as an entry receptor for infection of MPI cells, and production of type I interferon
Summary
Macrophages are a diverse population of innate immune cells. They function as a first-line defense against pathogens, including viruses. These macrophages differ by origin, repertoire of surface receptors and transcriptional regulation of many genes [1]. Macrophages are seeded into their tissue-resident environment during embryogenesis or differentiate from monocytes and develop plasticity and function in response to signals from their microenvironment [reviewed in 2, 3, 4]. Macrophages contain a broad array of surface receptors for recognition and engulfment of pathogens, including fungi, bacteria and viruses [5,6,7,8]. A key element of how macrophages function and elicit inflammatory signaling is that they bind to pathogens by their cell surface receptors
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